Integrated nanopore and paul trap mechanism for DNA capture and motion control

ABSTRACT

A mechanism is provided for capturing a molecule via an integrated system. An alternating voltage is applied to a Paul trap device in an electrically conductive solution to generate electric fields. The Paul trap device is integrated with a nanopore device to form the integrated system. Forces from the electric fields of the Paul trap device position the molecule to a nanopore in the nanopore device. A first voltage is applied to the nanopore device to capture the molecule in the nanopore of the nanopore device.

BACKGROUND

The present invention relates to nanopore devices, and morespecifically, to capture and control of molecules in nanopore devices.

Nanopore sequencing is a method for determining the order in whichnucleotides occur on a strand of deoxyribonucleic acid (DNA). A nanopore(also referred to a pore, nanochannel, hole, etc.) can be a small holein the order of several nanometers in internal diameter. The theorybehind nanopore sequencing is about what occurs when the nanopore issubmerged in a conducting fluid and an electric potential (voltage) isapplied across the nanopore. Under these conditions, a slight electriccurrent due to conduction of ions through the nanopore can be measured,and the amount of current is very sensitive to the size and shape of thenanopore. If single bases or strands of DNA pass (or part of the DNAmolecule passes) through the nanopore, this can create a change in themagnitude of the current through the nanopore. Other electrical oroptical sensors can also be positioned around the nanopore so that DNAbases can be differentiated while the DNA passes through the nanopore.

The DNA can be driven through the nanopore by using various methods, sothat the DNA might eventually pass through the nanopore. The scale ofthe nanopore can have the effect that the DNA may be forced through thehole as a long string, one base at a time, like thread through the eyeof a needle. Recently, there has been growing interest in applyingnanopores as sensors for rapid analysis of biomolecules such asdeoxyribonucleic acid (DNA), ribonucleic acid (RNA), protein, etc.Special emphasis has been given to applications of nanopores for DNAsequencing, as this technology holds the promise to reduce the cost ofsequencing below $1000/human genome.

SUMMARY

According to an embodiment, a method is provided for capturing amolecule via an integrated system. The method includes applying analternating voltage to a Paul trap device in an electrically conductivesolution to generate electric fields, and the Paul trap device isintegrated with a nanopore device to form the integrated system. Forcesfrom the electric fields of the Paul trap device position the moleculeto a nanopore in the nanopore device. The method includes applying afirst voltage to the nanopore device to capture the molecule in thenanopore of the nanopore device.

According to an embodiment, a system for capturing a molecule isprovided. The system includes a nanopore device including a nanopore anda Paul trap device integrated with the nanopore device to form anintegrated system. An alternating voltage is applied to the Paul trapdevice in an electrically conductive solution to generate electricfields. Forces from the electric fields of the Paul trap device positionthe molecule to the nanopore in the nanopore device. The nanopore devicehas a first voltage applied to capture the molecule in the nanopore ofthe nanopore device.

Additional features and advantages are realized through the techniquesof the present invention. Other embodiments and aspects of the inventionare described in detail herein and are considered a part of the claimedinvention. For a better understanding of the invention with theadvantages and the features, refer to the description and to thedrawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The subject matter which is regarded as the invention is particularlypointed out and distinctly claimed in the claims at the conclusion ofthe specification. The forgoing and other features, and advantages ofthe invention are apparent from the following detailed description takenin conjunction with the accompanying drawings in which:

FIGS. 1A through 1D illustrate views of fabricating a multilayerstructure for making an integrated nanopore and linear Paul trap systemaccording to an embodiment, in which:

FIG. 1A is a cross-sectional view of a multilayer structure for makingan integrated nanopore and linear Paul trap system;

FIG. 1B is a cross-sectional view of the multilayer structure whichshows the process to fabricate contact pads as conductive layers forsensing via the nanodevice and contact pads as conductive layers for thelinear Paul trap device;

FIG. 1C is a cross-sectional view showing that a nanopore is madethrough the layers of the multilayer structure; and

FIG. 1D is a top view of the multilayer structure showing contact padsfor the nanodevice and contact pads for the linear Paul trap device,which are connected to an alternating current voltage source.

FIG. 2 is a cross-sectional view of the multilayer structure of thenanopore device and the linear Paul trap device in an integrated system.

FIG. 3 is a method for capturing and sequencing molecules using theintegrated system of the nanodevice and the Paul trap device.

FIG. 4A illustrates how the Paul trap device positions and centers themolecule when voltage is applied with one polarity of the alternatingcurrent voltage source.

FIG. 4B illustrates how the Paul trap device positions and centers themolecule when voltage is applied with another polarity of thealternating current voltage source.

FIG. 5 is a block diagram that illustrates an example of a computer(computer setup) having capabilities, which may be included in and/orcombined with embodiments.

DETAILED DESCRIPTION

An embodiment provides a technique and a device to control DNA motionand enhance DNA capture rate into a nanopore by integrating the nanoporeand linear Paul trap together in a liquid environment of electricallyconductive solution. This nanodevice can be utilized for DNA and RNAsequencing.

The linear Paul trap is used in mass spectrometry to effectively trapsingle ion and charge molecules in a vacuum environment. In theembodiment, the linear Paul trap is utilized in the liquid environmentto trap single long strand DNA molecules, which is one of the steps tosequence the whole genome.

Accordingly, an integrated nanopore and linear Paul trap system in aliquid environment is discussed herein. This system can trap the longstrand DNA and/or RNA as well as enhance the capture rates of DNA andRNA into the nanopore. The linear Paul trap can capture and trap thesingle long strand DNA in certain range (e.g., in tens of nanometers).The nanopore (in nanometer size which is close to the diameter of DNAand RNA) can physically localize single strand DNA in the nanometerrange, providing enough dwelling time for identifying single bases.

Now turning to the figures, FIG. 1A is a cross-sectional view of amultilayer structure 100 for making an integrated nanopore and linearPaul trap system. The multilayer structure 100 may include a substrate101 such as silicon (Si) with 500 micrometer in thickness. Themultilayer structure 100 includes electrically insulating films 102,103, 105, and 107, and the insulating films may include silicon nitride(Si₃N₄). The thickness of them can vary from few to tens of nanometers.The insulating film 103 can be used as an etching mask for etchingthrough the substrate 101 via either dry or wet etching to form thewindow 180, and the etching stops on layer 102. As a result, part oflayer 102 will be a free-standing membrane. Layers 104 and 106 areelectrically conductive layers separated by electrically insulatinglayer 105. The conductive layer 104 can be 0.3 to few nanometers inthickness. The thickness of 106 can be tens of nanometers, like 20nanometers. The electrically conductive layers 104 and 106 are a metalsuch as titanium. The free-standing membrane part of 104 as describedabove is visible under a transmission electron microscope. To make ananometer size nanopore, FIG. 1C is a cross-sectional view to show thata nanopore 112 is made through the layers 102, 104, 105, 106, and 107via a transmission electron microscope, electron beam lithography, orother technologies.

FIG. 1B is a cross-sectional view of the multilayer structure 100 whichshows the process to fabricate contact pads as conductive layers 104 forsensing and conductive layer 106 for the linear Paul trap.

The windows (vias) 108 and 109 are opened through insulating layer 105,conductive layer 106, and insulating layer 107 down to the conductivelayer 104 (metal), and the windows 108 and 109 are contact pads used forsensing the difference for base pairs of the DNA molecule insidenanopore 112 by impedance, current, and/or other technologies asunderstood by one skilled in the art. They can be 5 micrometers by 5micrometers or up to hundreds of micrometers.

Windows 110, 111, 113, and 114 are the contact pads for the linear Paultrap system, and are opened down to conductive layer 106 (i.e., metal).Windows 113 and 114 are not shown in the cross-sectional view of FIG. 1Bbut are shown in the top view of FIG. 1D. The dimensions of them can be5 micrometers by 5 micrometers or up to hundreds of micrometers.

FIG. 1D is a top view of the multilayer structure 100 showing contactpads 108 and 109 for operating the nanopore device and contact pads 110,111, 113, and 114 for operating the linear Paul trap device.

Contact pads and windows may be used interchangeably because the metalis accessed through the open windows. The contact pads 110 and 111 areconnected to the same polarity of an alternating current (AC) voltagesource 150, and the contact pads 113 and 114 are connected to the samepolarity of the alternating current (AC) voltage source 150 which isdifferent from the contact pads 110 and 111.

In the embodiment, the insulating cap layer 107 is disposed so that theclassical linear Paul trap system/device can work with electricallyconductive solution 215 (shown in FIG. 2). The cap layer 107covers/shields the conducting layer 106 from the electrically conductivesolution 215 flowing in the nanopore 112 and protects the conductinglayer 106 from shorting out in the electrically conductive solution 215(i.e., blocks the circuit from being complete through the electricallyconductive solution 215) when voltage is applied by the alternatingcurrent voltage source 150. In one instance, the positive signal

$\left( {{+ \frac{1}{2}}V_{rf}{\cos\left( {\omega_{rf}t} \right)}} \right)$is applied to the conductive layer 106 in windows 110 and 111, while thenegative signal

$\left( {{- \frac{1}{2}}V_{rf}{\cos\left( {\omega_{rf}t} \right)}} \right)$is applied to the conductive layer 106 in windows 113 and 114. Thepositive and negative signals (i.e., polarity) continue to alternate asunderstood by one skilled in the art. As applied by the AC voltagesource 150, V_(r f) is the amplitude of rf signal and ω_(rf) is thefrequency of the rf signal.

FIG. 2 is a cross-sectional view of an integrated system/device 200 forcapturing and sequencing molecules, such as DNA and RNA molecules.Particularly, FIG. 2 is a schematic of the multilayer structure 100 ofthe nanopore device and the linear Paul trap device in the integratedsystem 200. In the integrated system 200, elements 101 through 112 ofthe multilayer structure 100 are the same as discussed above.

The multilayer structure 100 in the integrated system 200 of thenanopore and Paul trap device separates the electrically conductivesolution 215 into two reservoirs 213 and 214. The electricallyconductive solution 215 is only connected through the nanopore 112 forthe two reservoirs 213 and 214. Negatively charged DNA molecule 216 maybe in the reservoir 213. The alternating voltage of the alternatingvoltage source 150 is applied to the conducting layer 106 of the contactpads 110 and 111 (with one polarity) and the contacting layer 106 of thecontacts pads 113 and 114 (with another polarity); this produces avirtual focus point at the nanopore 112 which positions the DNA molecule216 at the nanopore 112. (The connections of the (metal) contact pads110, 111, 113, and 114 to the alternating voltage source 150 are notrepeated in FIG. 2 so as not to obstruct the view but are understood tobe present.) The negatively charged DNA molecule 216 can be pulledthrough the nanopore 112 by the voltage of a voltage source 220, andeach base of the DNA molecule 216 is illustrated as base 217. Thevoltage of the voltage source 220 is applied between the two reservoirs213 and 214 via two metal electrodes 218 and 219, for example Ag/AgCl.The voltage signal of the voltage source 221 is applied between the twosides of the conductive layer 104 through via widows 108 and 109. Thecurrent signals are detected by the current ammeter 222. When the DNAmolecule 216 is detected inside nanopore 112, the linear Paul trapsystem traps the DNA molecule 216 inside the nanopore 112 by thealternating voltage of the alternating voltage source 150. So the DNAbases 217 can be sensed and identified through current measured by theammeter 222 (and other technologies). In order to sequence the longstrand DNA or RNA, the voltage pulse signal can be applied from voltagesource 220 to move the DNA base 217 one by one out of the nanopore 112after the DNA molecule 216 is immobilized.

While the molecule 216 is in nanopore 112, a change in the current(measured via ammeter 222 which may be connected to/implemented in acomputer 500 in FIG. 5) is detected. The amount of change in themeasured current depends on the size and surface charge of therespective bases 217 of the DNA molecule 216. In this way, each base 217is sensed (i.e., sequenced) as it passes through nanopore 112 asunderstood by one skilled in the art.

FIG. 3 is a method 300 for capturing and sequencing molecules 216 usingthe integrated system 200 of the nanopore device and the Paul trapdevice.

At block 305, alternating voltage (also referred to as AC voltage) isapplied by the AC voltage source 150 to a Paul trap device in anelectrically conductive solution 215 (e.g., an electrolyte solution) togenerate electric fields, and the Paul trap device is integrated withinthe nanopore device to form the integrated system.

While the molecule 216 is in the electrically conductive solution 215 ofthe reservoir 213 (assuming that the DNA molecules 216 are first pumpedinto the reservoir 213), forces from the electric fields of the Paultrap device position the molecule 216 to the nanopore 212 in thenanopore device at block 310.

A first voltage is applied (via electrodes 218 and 219) to the nanoporedevice by the voltage source 220 to capture the molecule 216 in thenanopore 112 of the nanopore device at the block 315.

The method includes applying a second voltage (via voltage source 221connected to contact pads 108 and 109) to the nanopore device tosequence bases 217 of the molecule 216 in the nanopore 112.

The method in which the alternating voltage is applied (via AC voltagesource 150 connected to contact pads 110, 111, 113, and 114) to the Paultrap device prior to applying the first voltage (of the voltage source220) to the nanopore device.

The method in which the alternating voltage is applied to the Paul trapdevice while applying the first voltage to the nanopore device.

The method includes centering the molecule 216 to a location (e.g., themouth of the nanopore 112 in the reservoir 213) of the nanopore 112 inthe nanopore device by a combination of the forces of the Paul trapdevice (when alternating voltage of the AC voltage source 150 is appliedto contact pads 110, 111, 113, and 114) and the first voltage applied bythe voltage source 220 (via electrodes 218 and 219) to the nanoporedevice.

The method in which the Paul trap device comprises first pair of contactpads (also referred to as windows 110 and 111) and a second pair ofcontact pads (also referred to as windows 113 and 114), where thealternating voltage alternates polarity between the first pair ofcontact pads (which may have a positive polarity first then switch to anegative polarity) and the second pair of contact pads (which may have anegative polarity first then switch to a positive polarity). Theelectrically conductive solution 215 fills the two reservoirs (topreservoir 213 and bottom reservoir 214) connected by the nanopore 112.Insulating material layer 107 surrounds immersed parts of the first pairof contact pads (windows 110 and 111) and the second pair of contactpads (windows 113 and 114 shown in FIG. 1D) in the electricallyconductive solution 215 to prevent the first pair of contact pads(windows 110 and 111 opening to conducting layer 106) and the secondpair of contacts pads (windows 113 and 114 opening to conducting layer106) from conducting electricity through the electrically conductivesolution 215. Applying the alternating voltage (via the AC voltagesource 150) to the first pair of contact pads and the second pair ofcontact pads positions the molecule 216 to the nanopore 112 in one ofthe two reservoirs (e.g., the top reservoir 213) for capture below inthe nanopore 212. The forces, continuously changing (with the changingpolarity of the AC voltage source 150), act upon the molecule 216 toforce the molecule 216 into an equilibrium position centered at thenanopore 112, in order to prevent the molecule 216 from being moved outof position (out of position by being moved to the left or the right orout of position by being moved to the top or bottom (relative to FIG.1D)). The first voltage is applied to one electrode (e.g., electrode218) in one of the two reservoirs and another electrode (e.g., electrode219) in another one of the two reservoirs. The first voltage moves themolecule 216 through the nanopore 112 for sequencing respective bases217 of the molecule 216. The first voltage is turned off to sequence onebase 217 and turned on again to move to a next base 217.

FIGS. 4A and 4B further illustrate how the Paul trap device positionsand centers the molecule 216 in the reservoir 213. FIGS. 4A and 4B showa simplified version of the top view (shown in FIG. 1D) of themultilayer structure 100 within the integrated system 200, and thenanopore 112 has been enlarged for better viewing. Although not shownfor the sake of clarity, it is understood that missing elements fromFIG. 1D and FIG. 2 are understood to be present in FIGS. 4A and 4B.

FIG. 4A illustrates that the AC voltage source 150 applies positivevoltage (positive signal

$\left. \left( {{+ \frac{1}{2}}V_{rf}{\cos\left( {\omega_{rf}t} \right)}} \right) \right)$to the contact pads/windows 110 and 111, while applying negative voltage(negative signal

$\left( {{- \frac{1}{2}}V_{rf}{\cos\left( {\omega_{rf}t} \right)}} \right)$to contact pads/windows 113 and 114. In FIG. 4A, the electric fieldsflow from contact pads 113 and 114 to contact pads 110 and 111 with thenet effect shown by the electric field arrows E.

The forces acting upon the molecule 216 are shown by arrows F_(E)pointing inward from the top and bottom of the page to position themolecule 216 to the centered location of the nanopore 112. The forcesF_(E) are a result of the electric field E, and the forces F_(E) help tokeep the molecule 216 at the centered location even if the molecule 216moves around in the reservoir 213 before being captured in the nanopore112.

FIG. 4B illustrates that the AC voltage source 150 applies negativevoltage (negative signal

$\left( {{- \frac{1}{2}}V_{rf}{\cos\left( {\omega_{rf}t} \right)}} \right)$to contact pads/windows 113 and 114, while applying positive voltage(positive signal

$\left. \left( {{+ \frac{1}{2}}V_{rf}{\cos\left( {\omega_{rf}t} \right)}} \right) \right)$to the contact pads/windows 110 and 111. In FIG. 4B, the electric fieldsflow from contact pads 110 and 111 to contact pads 113 and 114 with thenet effect shown by the electric field arrows E.

In this case, the forces acting upon the molecule 216 are shown byarrows F_(E) both pointing outward to the top and bottom of the page toposition the molecule 216 to the centered location of the nanopore 112.

The constant forces FE shown in both FIGS. 4A and 4B (as the AC voltageof AC voltage source 150 alternates) center/hold the molecule 216 at thecentered location of the nanopore 112 (even against thermal motion andagitation), for capture in the nanopore 112. Voltage of voltage source220 can draw the positioned molecule 216 into the nanopore 112 forsequencing, and the AC voltage of AC voltage source 150 can be appliedduring sequencing of the molecule 216 to hold the molecule 216 in place(although the voltage source 220 is turned off during sequencing so thatthe molecule 216 does not traverse through the nanopore 112 until it istime to sequence the next base 217).

FIG. 5 illustrates an example of a computer 500 (e.g., as part of thecomputer setup for testing and analysis) which may implement, control,and/or regulate the AC voltage of the voltage source 150, the voltage ofthe voltage source 220, voltage of the voltage source 221, andmeasurements of the ammeter in the integrated system 200 as discussedherein.

Various methods, procedures, modules, flow diagrams, tools,applications, circuits, elements, and techniques discussed herein mayalso incorporate and/or utilize the capabilities of the computer 500.Moreover, capabilities of the computer 500 may be utilized to implementfeatures of exemplary embodiments discussed herein. One or more of thecapabilities of the computer 500 may be utilized to implement, toconnect to, and/or to support any element discussed herein (asunderstood by one skilled in the art) in FIGS. 1-4. For example, thecomputer 500 which may be any type of computing device and/or testequipment (including ammeters, voltage sources, connectors, etc.).Input/output device 570 (having proper software and hardware) ofcomputer 500 may include and/or be coupled to the nanodevices andstructures discussed herein via cables, plugs, wires, electrodes, patchclamps, etc. Also, the communication interface of the input/outputdevices 570 comprises hardware and software for communicating with,operatively connecting to, reading, and/or controlling voltage sources,ammeters, and current traces (e.g., magnitude and time duration ofcurrent), etc., as discussed herein. The user interfaces of theinput/output device 570 may include, e.g., a track ball, mouse, pointingdevice, keyboard, touch screen, etc., for interacting with the computer500, such as inputting information, making selections, independentlycontrolling different voltages sources, and/or displaying, viewing andrecording current traces for each base, molecule, biomolecules, etc.

Generally, in terms of hardware architecture, the computer 500 mayinclude one or more processors 510, computer readable storage memory520, and one or more input and/or output (I/O) devices 570 that arecommunicatively coupled via a local interface (not shown). The localinterface can be, for example but not limited to, one or more buses orother wired or wireless connections, as is known in the art. The localinterface may have additional elements, such as controllers, buffers(caches), drivers, repeaters, and receivers, to enable communications.Further, the local interface may include address, control, and/or dataconnections to enable appropriate communications among theaforementioned components.

The processor 510 is a hardware device for executing software that canbe stored in the memory 520. The processor 510 can be virtually anycustom made or commercially available processor, a central processingunit (CPU), a data signal processor (DSP), or an auxiliary processoramong several processors associated with the computer 500, and theprocessor 510 may be a semiconductor based microprocessor (in the formof a microchip) or a macroprocessor.

The computer readable memory 520 can include any one or combination ofvolatile memory elements (e.g., random access memory (RAM), such asdynamic random access memory (DRAM), static random access memory (SRAM),etc.) and nonvolatile memory elements (e.g., ROM, erasable programmableread only memory (EPROM), electronically erasable programmable read onlymemory (EEPROM), programmable read only memory (PROM), tape, compactdisc read only memory (CD-ROM), disk, diskette, cartridge, cassette orthe like, etc.). Moreover, the memory 520 may incorporate electronic,magnetic, optical, and/or other types of storage media. Note that thememory 520 can have a distributed architecture, where various componentsare situated remote from one another, but can be accessed by theprocessor 510.

The software in the computer readable memory 520 may include one or moreseparate programs, each of which comprises an ordered listing ofexecutable instructions for implementing logical functions. The softwarein the memory 520 includes a suitable operating system (O/S) 550,compiler 540, source code 530, and one or more applications 560 of theexemplary embodiments. As illustrated, the application 560 comprisesnumerous functional components for implementing the features, processes,methods, functions, and operations of the exemplary embodiments.

The operating system 550 may control the execution of other computerprograms, and provides scheduling, input-output control, file and datamanagement, memory management, and communication control and relatedservices.

The application 560 may be a source program, executable program (objectcode), script, or any other entity comprising a set of instructions tobe performed. When a source program, then the program is usuallytranslated via a compiler (such as the compiler 540), assembler,interpreter, or the like, which may or may not be included within thememory 520, so as to operate properly in connection with the O/S 550.Furthermore, the application 560 can be written as (a) an objectoriented programming language, which has classes of data and methods, or(b) a procedure programming language, which has routines, subroutines,and/or functions.

The I/O devices 570 may include input devices (or peripherals) such as,for example but not limited to, a mouse, keyboard, scanner, microphone,camera, etc. Furthermore, the I/O devices 570 may also include outputdevices (or peripherals), for example but not limited to, a printer,display, etc. Finally, the I/O devices 570 may further include devicesthat communicate both inputs and outputs, for instance but not limitedto, a NIC or modulator/demodulator (for accessing remote devices, otherfiles, devices, systems, or a network), a radio frequency (RF) or othertransceiver, a telephonic interface, a bridge, a router, etc. The I/Odevices 570 also include components for communicating over variousnetworks, such as the Internet or an intranet. The I/O devices 570 maybe connected to and/or communicate with the processor 510 utilizingBluetooth connections and cables (via, e.g., Universal Serial Bus (USB)ports, serial ports, parallel ports, FireWire, HDMI (High-DefinitionMultimedia Interface), etc.).

In exemplary embodiments, where the application 560 is implemented inhardware, the application 560 can be implemented with any one or acombination of the following technologies, which are each well known inthe art: a discrete logic circuit(s) having logic gates for implementinglogic functions upon data signals, an application specific integratedcircuit (ASIC) having appropriate combinational logic gates, aprogrammable gate array(s) (PGA), a field programmable gate array(FPGA), etc.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of onemore other features, integers, steps, operations, element components,and/or groups thereof.

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present invention has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Theembodiment was chosen and described in order to best explain theprinciples of the invention and the practical application, and to enableothers of ordinary skill in the art to understand the invention forvarious embodiments with various modifications as are suited to theparticular use contemplated

The flow diagrams depicted herein are just one example. There may bemany variations to this diagram or the steps (or operations) describedtherein without departing from the spirit of the invention. Forinstance, the steps may be performed in a differing order or steps maybe added, deleted or modified. All of these variations are considered apart of the claimed invention.

While the preferred embodiment to the invention had been described, itwill be understood that those skilled in the art, both now and in thefuture, may make various improvements and enhancements which fall withinthe scope of the claims which follow. These claims should be construedto maintain the proper protection for the invention first described.

What is claimed is:
 1. A method for capturing a molecule via anintegrated system, the method comprising: applying an alternatingvoltage to a Paul trap device in an electrically conductive solution togenerate electric fields, the Paul trap device being integrated with ananopore device to form the integrated system; wherein forces from theelectric fields of the Paul trap device position the molecule to ananopore in the nanopore device; and applying a first voltage to thenanopore device to capture the molecule in the nanopore of the nanoporedevice; wherein the integrated system comprises a first insulating layerdisposed on top of a substrate a first conductive layer disposed on topof the first insulating layer, a second insulating layer disposed on topof the first conductive layer, a second conductive layer disposed on topof the second insulating layer, and a third insulating layer disposed ontop of the second conductive layer; wherein a first pair of contact padsand a second pair of contact pads are each formed on the secondconductive layer, the alternating voltage alternating polarity betweenthe first pair of contact pads and the second pair of contact pads; andwherein the first pair of contact pads correspond to first windowsopened through the third insulating layer stopping on the secondconductive layer, the first windows being positioned on opposites sidesof the nanopore.
 2. The method of claim 1, further comprising applying asecond voltage to sequencing pads of the nanopore device to sequencebases of the molecule in the nanopore; wherein the second pair ofcontact pads correspond to second windows opened through the thirdinsulating layer stopping on the second conductive layer, the secondwindows being positioned on opposites sides of the nanopore; wherein thesequencing pads correspond to sequencing windows opened through thethird insulating layer, the second conductive layer, the secondinsulating layer, stopping on the first conductive layer.
 3. The methodof claim 1, wherein the alternating voltage is applied to the Paul trapdevice prior to applying the first voltage to the nanopore device. 4.The method of claim 1, wherein the alternating voltage is applied to thePaul trap device while applying the first voltage to the nanoporedevice.
 5. The method of claim 1, further comprising centering themolecule to a location of the nanopore in the nanopore device by acombination of the forces of the Paul trap device and the first voltageapplied to the nanopore device.
 6. The method of claim 1, wherein theelectrically conductive solution fills two reservoirs connected by thenanopore; and wherein insulating material surrounds immersed parts ofthe first pair of contact pads and the second pair of contact pads inthe electrically conductive solution to prevent the first pair ofcontact pads and the second pair of contact pads from conductingelectricity through the electrically conductive solution.
 7. The methodof claim 6, wherein applying the alternating voltage to the first pairof contact pads and the second pair of contact pads positions themolecule to the nanopore in one of the two reservoirs for capture in thenanopore; and wherein the forces, continuously changing, act upon themolecule to force the molecule into an equilibrium position centeredwith the nanopore, in order to prevent the molecule from being moved outof position.
 8. The method of claim 6, wherein the first voltage isapplied to one electrode in one of the two reservoirs and anotherelectrode in another one of the two reservoirs.
 9. The method of claim7, wherein the first voltage moves the molecule through the nanopore forsequencing respective bases of the molecule; and wherein the firstvoltage is turned off to sequence one base and turned on again to moveto a next base.